Water → 4-Chloro-6-methyl-2-[4-(3-nitro-benzyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1172519Notes

Reaction equation

HRID 1172519 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[CH3:12][O:13][C:14]([C:16]1[CH:17]=[C:18]([CH3:43])[C:19]2[O:25][C:24]3[C:26]([Cl:39])=[CH:27][C:28]([N:30]4[CH2:35][CH2:34][N:33](C5CC5)[CH2:32][CH2:31]4)=[CH:29][C:23]=3[CH2:22][S:21](=[O:41])(=[O:40])[C:20]=2[CH:42]=1)=[O:15].C([BH3-])#N.[Na+].O>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:12][O:13][C:14]([C:16]1[CH:17]=[C:18]([CH3:43])[C:19]2[O:25][C:24]3[C:26]([Cl:39])=[CH:27][C:28]([N:30]4[CH2:31][CH2:32][N:33]([CH2:7][C:6]5[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=5)[CH2:34][CH2:35]4)=[CH:29][C:23]=3[CH2:22][S:21](=[O:40])(=[O:41])[C:20]=2[CH:42]=1)=[O:15]

Participants

7

Reactant 4

HCID 962WaterHCID 74493-NitrobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 1317284884-Chloro-2-(4-cyclopropyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Product 1

HCID 1317284894-Chloro-6-methyl-2-[4-(3-nitro-benzyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Procedure

m-Nitrobenzaldehyde (0.456 g, 3.02 mmol) and titanium isopropoxide (1.23 mL, 4.12 mmol) were added to a solution of Example 125k (1.2 g, 2.75 mmol) in methanol (75 mL) and refluxed for 1.5 h. Sodium cyanoborohydride (0.188 g, 2.75 mmol) was then added to the reaction mixture at 30° C. and refluxed for 3 h. It was cooled, treated with water and filtered. The filtrate was extracted with chloroform. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, 5% methanol/chloroform) to obtain the title compound. Yield: 0.74 g (48%); 1H NMR (CDCl3): δ 2.6 (t, 4H, 2CH2), 2.63 (s, 3H, CH3), 3.22 (t, 4H, 2CH2), 3.63 (s, 2H, CH2), 3.9 (s, 3H, OCH3), 5.2 (s, 2H, CH2), 6.73 (s, 1H, Ar), 6.9 (s, 1H, Ar), 7.5 (t, 1H, Ar), 7.7 (d, 1H, Ar), 8.1 (s, 1H, Ar), 8.15 (d, 1H, Ar), 8.25 (s, 1H, Ar), 8.45 (s, 1H, Ar); MS: m/e (ES+) 573 (M+1).

Workup

  1. temperaturerefluxed for 1.5 h
  2. temperaturerefluxed for 3 h
  3. temperatureIt was cooled
  4. filtrationfiltered
  5. extractionThe filtrate was extracted with chloroform
  6. washThe organic layer was washed with water, brine
  7. customdried
  8. concentrationconcentrated
  9. custompurified

Sources & evidence

ORD record
ord-4b605d3a6a5b44f988274a4da9577181
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

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